Derivatives of sapogenins and their preparation



Patented Jan. 18, 1944 f v i i 2;

UNITED STATES PATENT OFFICE] DERIVATIVES, or SAPOGENINS AND THEIR.

PREPARATION Russell Earl Marker, State College, Pa., assignor to Parke, Davis & Company, Detroit, Mich, a

J corporation of Michigan 'No Drawing. Original application March 8, 1941, Serial No. 382,450, now Patent No. 2,289,373, dated July 14, 1942. Divided and this application November 3, 1941,'Serial No. 411,738 V "19 Claims. ('01. zoo-397.2) v This invention relates to steroidal'hormone-inthe number of substituents attached to' these" termediates and preparation of the same, and, rings. v I more particularly, to the preparation of new These diflerences are shown below: steroidal sapogenin derivatives useful as-interme- I diates for the manufacture of hormones. v 5

This application is a division of my copending application. Serial No. 382,450, filed March 8, 1941 and is a continuation-impart of my copending application, Serial No. 317,419, filed February 5, 1940. 10

One of the objects of this invention is to prepare new steroidal sapogenin derivatives which can readily be converted to pregnane derivatives which in turn are readily convertibleintohormones such as those having progestational and cortical activity.

Other objects will be apparent from a perusal of this specification. I

The steroidal sapogenins have, in general, the formula CnHMOs-s, of which the portion CsHieO: .20 is known to be present as a side chain attached too ring D of the steroid skeleton. Tschesche-and Hagedorn (Bel-.68, 2247 (1935)) proposed the for the sapogenin, tigog'enin, and later workers have, with reservations, accepted this formulation of the steroidal sapoge'nin side chain. Other 60 .sapogenins such as digitogenin, gitogenin, chlorogenin, diosgenin, and sarsasapogenin have been shown to differ from tigogenin only in'regard to the connections between ring A and B,

the degree of saturation of the ring system, and M structure for the side chain of these steroidal sapogenins'is that shown below.

It is apparent that this formulation difl'ers from that of Tschesche and Hagedorn in that the linkage, C2':O-, is transferred from C2: to C22.

However, a profound difference in'the nature of the functional character of the sidechain oxygen atoms is implied. for while the Tschesche-Hagedorn formula is that of an a,a-di-tetrahydrofuryl derivative, the Marker-Rohrmann' formula is that of a spiro-ketal.

For the purpose of greater clarification, the Marker-Rohrmann formulation of the side chain of the steroidal sapogenins will be used in'describing the invention. It is to be understood, however, that the processes and products of the present invention may be obtained by the use of the methods herein to be described and these processes and products are claimed without any implications that the reactions and structures involved will ultimately be proved to be as represented herein. a

It is known that when steroidal sapogenins such as sarsasapogenin, chlorogenin, etc., are refluxed at atmospheric pressure with acetic anhydride, the nuclear hydroxyl groups are acetylated, and the simultaneous occurrence of any other transformation has never been described. Thus, there are obtained sarsasapogenin acetate, chlorogenin diacetate, etc., of the formulae,

J) 0 C C H:

Chlorogonln diacetate These acetylated steroidal sapogenins may be hydrolyzed, e. g. with acid or alkali, to regenerate the original sapogenins. Likewise, when p-nitrobenzoyl chloride and pyridine, succinic anhydride and pyridine, or other common acylating methods have been employed, the corresponding acylated sapogenins have been obtained, and it has been possible to hydrolyze these to the original sapogenius.

I have found, however, that when the steroidalsapogenins are reacted with acidic agents, for example, with acylating agents such as acid anhydrides, under conditions more vigorous than those required merely for acylation, that new acylated steroidal sapogenin derivatives are formed which are not identical with acylated sapogenins obtained from the same reactants under milder conditions. The new compounds, on hydrolysis with alkali, do not regenerate the original steroidal sapogenins, but instead yield compounds isomeric with the sapogenins, I therefore designate the new free hydroxylic compounds as pseudosapogenins, (abbreviated;

zp-genins).

From the properties of my new 4/-sapogenins and their esters, it appears that they have, attached to ring D, a new, altered, side chain of the probable formula CBHl5 O(X), which may be of one of the following types,

where X is hydroxyl in the case of the pseudosapogenins, and an acyloxy group in the case of the acylated pseudo-sapogenins.

The pseudo-sapogenins are characterized by the fact that they contain a new type of side chain which undergoes distinctive reactions. Thus the pseudo-sapogenins are unsaturated to bromine and therefore readily decolorize a solution of bromine in acetic acid. On treatment with acids, for example, with alcoholic hydrochloric acid, the pseudo-sapogenins are isomerized to the corresponding steroidal sapogenins. The side chain of the pseudo-sapogenins contains a reactive hydroxyl group which may be acylated, for example, acetylated.

The pseudo-sapogenins may also be characterized as steroidal sapogenin derivatives having attached to the steroidal ring D a side chain of formula CBH15OX which may be represented structurally as,

copending application, Serial No. 393,667, filed May 15, 1941.

Now I have found that the pseudo-sapogenins can be reduced, for example, catalytically hydrogenated, to give a class of substances which conbath. The white crystals which separate are collected, washed with ether, and recrystallized from tain two more hydrogen atoms in the side chain and which may therefore be designated as exodihydro-pseudo-sapogenins. The exo-dihydropseudo-sapogenins thus have attached to the steroidal ring D a side chain of. formula V CsHnO-X which may be represented structurally as where X is a member of the class hydroxyl and groups capable of hydrolysis to give hydroxyl.

In contrast to the pseudo-sapogenins the exo-dihydro-pseudo-sapcgenins are not affected by alcoholic hydrochloric acid. Like the pseudosapogenins, 'however, the exo-dihydro-pseudosapogenins show unsaturation to bromine in aceticacid and contain in the side chain a reactive hydroxyl group which may be acylated. for example, acetylated. The structure in the side chain of these exo-dihydro-pseudo-sapogenins is not shown with certainty. It is believed, however, that most'of the reactions of these substances may be explained by one of the following structures for the side chain at tached to ring D:

CH: CH: ('JH- CH CH:- CH: H- CHiOH The exo-dihydro-pseudo-sapogenins and their exo-acylates are useful in that they are very readily oxidized under mild conditions with formation of d -unsaturated-20-keto-pregnane compounds having in ring D the structure CH3 CH3 I This type ofv oxidation is described in greater detail in my' copending application, Serial No. 382,450, filed March 8, 1941.

My inventionmay be further illustrated by the following examples:

Example 1 The syrup remaining behind is Found: C, 77.3; H, 10.9.

ethyl acetate, giving needles of M. P.'170-173-" C.

, This is pseudo-sarsasapogenin,

(b). A mixture of 1 g. of pseudo-sarsasapogenin,

500 mgs. of Adams platinum oxide catalyst and 120 cc. of acetic acid is shaken with hydrogen at three atmospheres pressure and at room temat 154-16? C. This new product, is therefore notidentical with the starting material nor with the dihydro-sarsasapogenin obtained by hydrogenating sarsasapogenin in acidic solution. Therefore, it is called exo-dihydro-pseudo-sarsasapogenin. The same product may be obtained by conducting the hydrogenation inabsolute alcohol instead of in acetic acid.

Anal. Calcd. for CZ'IH4603I C, 77.4; H, 11.1

A sample of exo-dihydro-pseudo-sarsasapog enin is heated for a short time at 60 C. with p-nitrobenzoyl chloride and pyridine. The-mix ture is poured into dilute hydrochloric acid and;

the precipitate collected and recrystallized from ethyl acetate giving white needles, M. P. 196-197 C. This substance is the bis-p-nitrobenzoate oi exo-dihydro-pseudo-sarsasapogenin. l w

Five grams of exo-dihydro-pseudo-sarsasapogenin are refluxed with 50cc. of acetic anhydride for one-half hour. The excess acetic anhydride is removed in vacuo and the residual syrup .crystallized from pentaneto give; white needles, M. P.

. 95 C., of exo-dihydro-pseudo-sarsasapogenin diacetate.

Instead of acetylating exo-dihydro-pseudosarsasapogenin to obtain exo-dihydro-pseudosarsasapogenin' diacetate, the latter may also be prepared by hydrogenating pseudo-sarsasapog-'-" enin diacetate.

Example 2 V This product, which is 'pseudo-sarsasapogenin, forms a crystalline bis-p-nitrobenzoate which may be crystallized from. acetone as pale yellow crystals, M. P; 156.5-159" C.

,Pseudo-sarsasapogenin diacetate is prepared by refluxing 2.5 g. of pseudo-sarsasapogenin for thirty minutes with 15 cc. of acetic anhydride and then removing the acetic anhydride by evaporation in'v'acuo. The residual oil is pseudo-sarsaand it may be crystallized sapogenin diacetate only with difliculty (b). To 1 g. of pseudo-sarsasapogenin diacetate in cc. of acetic acid is added 0.2 g. of platinum Example 3 (a). A mixture of 2.5g. of chlorogenin and ccuof acetic anhydride is heated at 200 C. for

ten hours. The acetic anhydride is then evaporated in vacuo and the syrupy residue hydrolyzed with hot alcoholic potassium hydroxide. The small'white crystals which separate on dilution are collected and washed well with alcohol. The

product thus obtained is pseudo-chlorogenin and after recrystallization from acetone has the M. P. 268-2'l0 C. i It gives a large depression in M. P. with" a sample of chlorogenin. The substance is very sparingly soluble in acetone, ethyl acetate, ether, alcohol and similar solvents.

'(b). A solution 01 2g. of pseudo-chlorogenin in 300 cc. of acetic acid is mixed with 0.5 g. of platinum oxide catalyst, and the suspension shaken in a hydrogen atmosphere at room temperature and40lbs. pressure for three hours. Then the mixture is filtered, and the filtrate evaporated to dryness. The residue is crystallized from alcohol and thus gives exo-dihydro-pseudo-chlorogenin, M. P. 270 C. This substance gives'a depression in M. P. with pseudo-chlorogenin which also has M. P. 270 C. I

(c). A mixture of 1 g. of exo-dihydro-pseudochlorogenin andlO, cc. of acetic anhydride is refluxed for a'hali hour. Then the excess acetic anhydride is removed in vacuo and the residue crystallized from methanol to give pure exo-dihydro pseudo chlorogenin triacetate, M. P.

Example! for seventeenhours. Then the catalyst is iiltered ofiandthe filtrate concentrated in vacuo. Since a certain amount of acetylation occurs during the above operations, this crude product is best hydrolyzed before attempting to crystallize it. For this purpose, the residue is refluxed for ten minutes with an excess of 3% ethanolic potassium hydroxide solution. Then the mixture' is diluted with water and the precipitated product collected and crystallized from acetone to give white needles, M. P.7l-137" C., or exodihydro-pseudo-epi-sarsasapogenin.

One hundred mgs. of exo-dihydro-pseudo-episarsasapogenin is warmed for an hour at 60 C. with 200 mgs. of p-nitrobenzoyl chloride and 3 cc. of pyridine. Then themixture is poured into dilute hydrochloric acid and the precipitate collected. "After crystallization from-acetone, there is obtained the characteristic exo-dihydropseudo-epi-sarsasapogenin di-p-nitrobenzoate as white needles of M. P. 207-2090.

withhot ethanolic potassium hy- 1 g. of platinum'oxide catalyst and 150,

(0) A solution of 4.16 g. of exo-dihydropseudo-epi-sarsasapogenin in 20 cc. 0! acetic anhydrideis refluxed for thirty minutes. Then the excess acetic anhydrid is removed by distillation in vacuo. The residual exo-dihydro-pseudo-episarsasapogenin diacetate may be purifledby recrystallization. However, it is sufficiently pure for most purposes.

Example .5

(a). A mixture 0! 3.6g. 0! tigogeninand 25 cc. of acetic anhydride is'heated at 195-200 C. for eight hours. The solvent is removed in vacuo and the residue hydrolyzed with ethanolic potassium hydroxide. The neutral material is crystallized from aqueous acetone-to give white crystals of pseudo-tigogenin having M. P. 193- 196 C.

(b). To a solution of 500.mgs. of pseudo-tigogenin in 50 cc. of glacial acetic acid is added 250 mgs. of platinum oxide catalyst. The mixture is shaken with hydrogen at-45 lbs. pressure for twenty hours. Then the catalyst is removed by filtration and the filtrate concentrated to a small volume. on cooling, a crystal crop separates. This crop is collected and recrystallized from acetic acid and from ether to give exo-dihydropseudo-tigogenin of M. P. 202-205 C. It is very insoluble in acetone and ether.

The same exo-dihydro-pseudo-tigogenin is obtained by hydogenating pseudo-diosgenin or pseudo-tigogenone according to the procedure outlined in the above paragraph.

In contrast to'pseudo-tigogenin, exo-dihydropseudo-tigogenin. is recovered unchanged after refluxing for two hours with-alcoholic hydrochloric acid. Both pseudo-tigogenin and exo- .dihydro-pseudo-tigogenin readily decolorize bromine in acetic acid.

Example 6 (a). A mixtureoi 9 g. of desoxysarsasapogenin and 40 cc. of acetic anhydride is heated'in a sealed tube for ten hours at 200 C. Then the acetic anhydride is evaporated in vacuo and the I residue hydrolyzed by refluxing it with an excess of alcoholic potassium hydroxide for thirty minutes. The mixture is diluted with water and the product extracted with ether. After removing the ether on a steam'bath the residue is crystallized from aqueous acetone to give pseudodesoxysarsasapogenin or M. P. 130 C.

(b). A mixture of 600 mgs. of pseudo-desoxysarsasapogenin, 200 mgs. of platinum oxide catalyst and cc. of glacial acetic acid is shaken with hydrogen at room temperature and a pressure of three atmospheres for sixteen hours. Then the mixture is filtered and the solvent evaporated in vacuo. The residue is hydrolyzed by refluxing it for a short time with methanolic potassium hydroxide solution. The hydrolyzed mixture is diluted with water, extracted with ether and the ethereal extract washed well with water. The ether is removed on the steam bath and the residue is crystallized from'the acetone to give exo-dihydro-pseudo-desoxysarsasapogenin of M. P. 128-129 C. A mixture with pseudodesoxysarsasapogenin melts at -112 C. proving their non-identity.

Example '7 (a). Tigogenone is prepared by the oxidation of tigogenin with chromic anhydride in acetic acid at room temperature according to the method of Jacobs and Fleck, J. Biol. Chem, 88, 548 (1930).

(b). Epi-tigogenin is prepared from this as follows: A mixture of 20 g. of tigogenone, 20 g. of aluminum isopropylate and 500 cc. of dry isopropyl alcohol is refluxed on a steam bath for eight hours. Then the mixture is slowly distilled through a short column over a period of four hours to a small volume. To this residue is added 20 g. of potassium hydroxide in 500 cc. of methanol and the whole is refluxed for fifteen minutes. Then the mixture is poured into water and acidified with hydrochloric acid. The precipitated solid is removed by extraction with ether and the ethereal extract thus obtained is washed well with water. The ethereal extract is evaporated to dryness on the steam bath and the residue dissolved in 1 liter of 95%-alcohol. To this is added a boiling solution of 40 g. of digitonin in 3 liters of 95% alcohol. After standing for three hours at room temperature, the precipitated digitonide is collected and washed with alcohol. The alcoholic filtrate is concentrated to a volume of 500 cc. and 4 liters of ether are added. A small precipitate is filtered off and the ethereal filtrate washed well with water. Then the ethereal solution is evaporated to dryness on a steam bath and the residue crystallized from acetone, methanol, and ethylacetate to give epitisoeenin of M. P. 242-245 C.

A solution of 100 mgs. of the above epi-tigogenin is refluxed with 5 cc. of acetic anhydride for so thirty minutes. On cooling, the acetate of epitigogenin separates in the form of needles. These are collected, recrystallized from methanolacetone and then have M. P. 199-202 C.

(c). A mixture of 10 g. of epi-tigogenin and as cc. of acetic anhydride is'heated in a sealed tube for ten hours at 200 C. Then the tube is opened and the excess acetic anhydride removed by distillation in vacuo. The residue is crude pseudo-epi-tigogenin diacetate and it may be purified by crystallization from ether-pentane.

The whole of the pseudo-epi-tigogem'n diacetate obtained as described above is hydrolyzed by refluxing it for thirty minutes with an excess of alcoholic potassium hydroxide solution. The hydrolysate is diluted with water and the product isolated by extraction with ether and then evaporating the etheral extract. The residue is crystallized from ether-pentane, and dilute acetone to give needles of pseudo-epi-tigogenin of M. P. 148-150" C.

(d). A mixture of 1 g. of pseudo-epi-tigogenin, 500 ings. of Adams platinum oxide catalyst and 100 cc. of glacial acetic acid is shaken with hydrogen at three atmospheres pressure at room to temperature. for twelve hours. Then the catalyst is filtered ed and the filtrate evaporated in vacuo. The residue is crystallized from ether, acetone and finally methanol. As thus obtained the product, exo-dihydro-pseudo-epi-tigogenin, 50 forms long needles of M. P. 193-196 C.

One gram of exo-dihydro-pseudo-epi-tigogenin is refluxed with 10 cc. of acetic anhydride for thirty minutes. The excess acetic anhydride is acetic anhydride is evaporated in vacuo to leave,

a residue which crystallizes after cooling. This pseudo-diossenin diacetate.

(b). A solution of 5 g. of pseudo-diosgenin diacetate in 500 cc. of acetic acid is shaken with 500 mgs. of platinum oxide catalyst under hydrogen at a pressure of three atmospheres for six hours. Then the catalyst is removed by filtration and the filtrate evaporated in vacuo. The residue is crystallized from methanol, thereby yielding exo-dihydro-pseudo-tigogenin diacetate of M. P. 122-124" c. 7

Exo-dihydro-pseudo-tigogenin diacetate may also be prepared by hydrogenating pseudo-tigegenin diacetate orv pseudo-tigogenone acetate or by acylatine exo-dihydro-pseudo-tigogenin.

' The foregoing examples. illustrative of my inventlon. are suo ect to numerous variations in reaard to the reactants employed, the conditions of reaction, the modes or removing the products rrom' reaction mixtures, and the like. All Of these variations, herein described and claimed, fall witmn the scope of my invention. i

The reduction or the pseudo-sapogenin compound is conveniently accomplished by shaking the pseudo-sapogenin, or an esterthereor, with piatmum oxide catalyst in acetic acid in the presence of a slight pressure of hydrogen at about room temperature. The platinum. oxide cata yst is prepared according to the directions of Organic Syntheses, \ILLI, ex ed. by R. Adams (Wiley,

N. Y. (3., 192a). In reality, the actual catalyst is platinum metal in a particularly active form, since the platinum oxide is reduced to this under the conditions of hyarosenation.

Instead oi using platinum oxide as a catalyst, other catalysts sucn as platinum black, ltaney nickel or the various base metal oxide catalysts such as copper chromite may be used with satisi'actory results. Instead of using acetic acid as a solvent in the reduction. other organic solvents inert to catalytic hydrogenation such as 81601101 or ethyl acetate may be used with as satisfactory results.

In general, any pseudo-sapogenin or an exoacylate thereof can be reduced in the side chain according to my invention to form an exo-di-, hydro-pseudo-sapogenin or exo-acylat thereof; since I have found that this reduction is a characteristic reaction of the pseudo-sapogenin side chain, and proceeds independently or structural features in other portions of the molecule. as for example in rings A and B. When pseudo-sapogenins, or exo-acylates thereof, containing re-- ducible groups either in rings A and/or B, or in substituents attached thereto. are reduced to form I exo-dihydro-pseudo-sapongenin compounds the said reducible groups are transformed during the process. The most frequently encountered reducible groups may be tabulated together with. their transformation products as follows:

removed by distillation in vacuo and the residue 05 Reducible I Group formed on reduction is crystalhzed from methanol to give exo-dihydro- I pseudo-epi-tigogenin diacetate, M. P. 1.18-121 C. Kama group secondary alcohol The same exo-dihydro-pseudo-epi-tigogenin sm y cramp Primary alcohol d diacetate may be obtained by hydrogenating ggigtggt. i h? eompoun pseudo-epl-tizozenin diacetate. 7o :gigNHa Example 8 IQHOT C. for six to fifteen hours. Then the Examples of transformations of this sort have I already been given. For-instance, pseudo-dios-- geuin, pseudo-tiaosenone and M-pseudo-tiamgenenone yield, on reduction the same product that pseudo-tigosenin yields, namely, exo-dihydro-pseudo-tlsosenin.

When the nucleus of compound to be' reduced contains only substituents u m c edbv ca l t c h o n on, h

400mm and cONflathen' the ex'o dihydro- -ps eudo sapogeninjcompound'formed wiil'con-- 1 that my invention com tainthesamegrouplngs;

It will be appreciated prehends-th'ese newipseudo-sapogenin reduction products which I have desig ated as exo-dihydro-Y pseudossapogenin compounds. ,These new sub' stances-arecharacterized by containing, in the steroid skeleton only such groupings as are unaiiected by 'catalytichydrogenation under conditions which; reduce 'pseudo-sapogenins to exodihydro-pseudo sapogenins; and'they are further characterized by'having in the side chain attached toringDthestructure,

1 on. p

where x is amember oi the class consisting OH and groups hydrolyzable to OH.

A particularly useful class of exo-dihydropseudo-sapogenin compounds may be represented by the formula,

where Y1, Y2 and Y: are members of the'class consisting oi on H 3 H and groups hydrolyzable to and where Xis a member of the class consisting of -OH and groups hydrolyzable to OH. These compoundsare especially easily obtained since the sapogenins from which they are derived are themselves readily available.

Some oi these parent sapogenins occur in nature in the form 01 saponins while the rest, oiothese parcnt-sapogenins are readily prepared from the saponins by. simple transformations. s I

The GXOrrdlhYdIO-PSGHdO-S3PO88I11BS contain a reactive hydroxyl group in the side chain. I have found that it is possible to acylate this hydroxyl group by treating the exo-dihydropseudo-sapog'enin with an acylating agent as illustrated in the above examples. Suitable acylating' agents other than those indicated in theexamples-include benzoyl chloride, furoyl chloride, butyric'anhydridqketene or, in general,

other acidanhydrides, acid halides and the like.

The exo-dihydro-pseudo-sapogenin compounds acylated at the exo-hydroxyl group can be hydrolyzed by treatment wtih hydrolytic the pseudo-sapogenin -structure' agents such as alkaline or acidic reagents. Such hydrolytic agents include aqueous sodium hydroxide, alcoholic hydrochloric acid and the like.

What I claim as my invention is: 1. The process which comprises reducing a pseudo-sapogenin compound having in ring D the ,where Xis aimemlber oi the class hydroxyl and groups capable of alkaline hydrolysis to give hydroxyl, with production of an 'exo-dlhydropseudo sapogenin compound having in ring D the structure 2. The process which comprises reducing a pseudo-sapogenin, thereby producing an exoidihydro-pseudo-sapogenin. V

7 sapogenin exo-acylate.

8. The process which comprises subjecting a pseudo-sapogenin compound or the formula where Yr, Y: and Y: are members 01 the class consisting, oi

. on 11 -0 v n and groups hydrolyzable to s on where X is a member of the class consisting of -OH and groups capable of alkaline hydrolysis to -OH. where nA represents n double bonds, n having one or the values 0 and 1, to catalytic exo-dihydro-pseudohydrogenation, with production of an exo-dlhydro-pseudo-sapogenin compound of the formula where Y1, Y: and Y: are members of the class consisting of and groups hydrolyzable to 9.The process for preparing an exo-dihydropseudo-sapogenin compound of the formula where X is a member of the class consisting of I -OH and groups capable of alkaline hydrolysis 'to -OH," which comprises subjecting a pseudoszi'pogenin compoundoi the formula CH: CH!

' i Jeane-x."

to catalytic hydrogenation in the presence of a platinum catalyst.

10. An exo-dihydro-pseudo-sapogenin compound characterized by containing in the steroid skeleton only such substituents as are unafiected by catalytic hydrogenation under conditions which reduce pseudo-sapogenins to exo-dihydropseudo-sapogenins, and further characterized by having in the side chain attached to ring Dthe structure,

and groups hydrolyzable where x is a member of the class consisting of --0H and group hydrolyzable to '--OH.

- 11. An exo-dihydro-pseudo-sapogenin comi H pound of the formula where Y1, Y: and Y: are members of the consisting of on n and where X is a member of the class consisting of OH and groups capable of alkaline hydrolysis to -OH. a 1

12. Exo-dihydrc-pseudo-sarsasapogenin melting at approximately 168-1'70 C. and forming a bis-p-nitrobenzoate melting at approximately 196-19.7 C.

13'. 'IEIm-dihydro-pseudo-chlorogenin melting at approximately 270 C. and forming a triacetate melting at approximately C.

14. Exo-dihydro-pseudo-tigogenln approximately 202-205 Chand forming a diacetate melting at approximately 122-124: C.

15. Process according to claim 1 in which the reduction is effected by catalytic hydrogenation in the presence of a platinum catalyst.

16. Process according to claim 6 in which the hydrogenation is effected in the presence of a platinum catalyst.

17. Process according to claim '7 in which the hydrogenation is eflected in the presence of. a platinum catalyst.

18. Process according to claim 8 in which the hydrogenation is effected in the presence of a platinum catalyst.

a. 19. The process for preparing exo-dihydropseudo-'sarsasapogenin which comprises catalytically hydrogenating pseudo-sarsasapogenln in the presence of a platinum catalyst.

' RUSSELL EARL MARKER.

class melting at i 

